We plan to continue studies on the mechanisms for regulation of transcription and balanced globin synthesis during erythroid development using the mouse spleen as a model system. These studies will include: 1) elucidation of the post-transcriptional addition of the 5'-"cap" to the alpha and beta mRNA, 2) quantitation of beta mRNA and alpha mRNA in polyribosomes at various stages of splenic erythropoiesis, and 3) determination of the degradation rates of the globin mRNAs. We propose to study the switching from gamma-chain to beta-chain synthesis in late fetal development in the fetal sheep. These studies will include assays of alpha, beta, and gamma mRNA amounts and synthesis at various times using specific complementary DNA probes. Attempts will be made to manipulate further the timing of the switch to beta-chain synthesis during fetal development. BIBLIOGRAPHIC REFERENCES: Kazazian, H.H., Jr., Ginder, G.D., Snyder, P.G., VanBeneden, R.J., and Woodhead, A.P.: Quantitative deficiency of chain-specific globin mRNA in the thalassemia syndromes. Proc. Nat. Acad. Sci. USA 72: 567-571, 1975. Cheng, T.C., Polmar, S.K., and Kazazian, H.H., Jr.: Isolation and characterization of modified globin messenger RNA from erythropoietic mouse spleen. J. Biol. Chem. 249: 1781-1786, 1974.